A statistical analysis by the World Health Organization (WHO) indicates that more than 220 million people have to live with diabetes (1). Diabetes caused over 1.1 million deaths in 2005, and 4 million in 2011. Estimates show that 4.8 million people died in 2012 from complications of the disease, with people under 60 accounting for half the deaths (www.cbsnews.com/8301-204—162-57549731/371-million-people-have-diabetes-globally-about-half-undiagnosed/). Early diagnosis, on time treatment, and continuous management are vital to ensure patients' quality of life and to avoid circulatory problems and diseases caused by diabetes, such as kidney failure, heart disease and blindness (1-2). Current practice for diabetes management relies on monitoring blood glucose. There is a general dislike of the pain and inconvenience caused by finger pricking, leading to fewer tests and inadequate blood glucose control, which in turn results in more complications from the disease and significantly increased case management costs. Repeated painful finger sticks are a major problem for young children, and has similar negative consequences on disease management. Furthermore, finger pricking also can cause fainting and blood-borne infection (3-5).
Glucose sensing dates back to 1841 with glucose detection in urine, but the correlation between urine and plasma glucose has been shown to be inconsistent (6). There are currently many different glucose meters on the market for measuring blood glucose. However, to use these devices, patients have to prick their finger for a drop of blood multiple times a day. Other techniques have been developed which employ minimally invasive or noninvasive techniques for blood glucose monitoring, including infrared (IR) spectroscopy (7-9), fluorescence spectroscopy (10-11), Raman spectroscopy (12-13), optical polarization rotation measurement (14-17), photo-acoustic probes (18), and surface plasmon resonance (19-20). Results from these techniques are limited by spectral signal-to-noise levels and sample thickness, and have to be correlated with direct blood glucose measurements. While methods based on optical measurements are available (see, e.g., the OrSense NBM device described at www.orsense.com/files/files/Journal of Diabetes Science and Technology.pdf), most are for laboratory use only and are not suitable for routine glucose monitoring at home due to the size, cost, and complexity of operation of the required equipment. One instrument based on the detection of glucose in human sweat has been marketed for diabetes diagnosis. However, the difficulty of use due to the sweat collection process and the level of accuracy have resulted in its removal from the market. Another product detects blood glucose concentration via an optical method called “occlusion spectroscopy” (21). However, for reasons of cost and simplicity of operation there remains a need for a convenient, easy to use, and low cost glucose sensor.
Many studies have demonstrated that there is a correlation between blood glucose and saliva glucose levels (22-26). The application of saliva glucose measurements directly to indicate the health conditions of an individual is theoretically possible and appears realistic. It is reported that salivary glucose levels are significantly higher in diabetic patients than in people without diabetes under similar conditions (27-29). Thus, measurement of saliva glucose level can be utilized as an alternative diagnostic method for diabetics and as a health indicator of a subject who is normal or suspected of having diabetes. There are reported measurements of glucose in saliva using optical measuring systems such as a liquid chromatography-mass spectrometer (LC-MS) or a UV-visible spectrophotometer (22, 24-26). However, the cost of the instruments is very high and their operation is complicated and time consuming, making them unsuitable for everyday personal use. Therefore, these methods cannot be used for individual glucose monitoring at home or in the course of daily activities. Until now, there has not been a suitable technology for home measurement of glucose using saliva because there wasn't an easy to use, low-cost sensor system sensitive enough to detect the low levels of glucose present in saliva.